In this Phase II STTR project, Vestan Medical Imaging, Inc. will complete the development and clinical evaluation of its proprietary formulation of a fluorescent drug and new medical devices for Sentinel Lymph Node (SLN) biopsy for the surgical treatment of melanoma and breast cancer. Vestan will partner with the University of Utah Huntsman Cancer Institute (HCI) through a Subaward to conduct two Phase I/II clinical trials in patients undergoing a SLN biopsy for malignant melanoma or breast cancer. The FDA has granted IND- exempt status for each trial. Both studies have been reviewed and approved by the Univ. of Utah IRB. HCI and the Univ. of Utah serve a 7-state geographic region that includes UT, MT, ID, WY, eastern NV, western CO, and northern AZ. The geographically large patient service area and outreach programs to Hispanic and nearby Native American population centers enable these hospitals to accrue patients on clinical trials quickly, and with a study population that reflects the ethnic diversity of this large geographic region. The Specific Aims to complete the development and evaluation of this new method of SLN biopsy are: (1) Stability testing of the fluorescent drug formulation and determination of the drug clearance rate through pharmacokinetic studies. (2) Produce a sufficient number of prototype illumination and visualization devices for use in the 2 clinical trials. (3) Conduct two Phase I dose-escalation studies of subdermally- or intradermally-injected 0.001% to 1% fluorescent dye in 20 patients undergoing a SLN biopsy procedure in the treatment of malignant melanoma and in 20 patients undergoing a SLN biopsy procedure for breast cancer. (4) Conduct two statistically-robust Phase II clinical trials of the fluorescent dye and visualization devices in 80 patients undergoing SLN biopsy for malignant melanoma and 80 patients undergoing SLN biopsy for breast cancer. (5) Vestan will develop and disseminate an educational program on the benefits of using a fluorescent dye in SLN biopsy procedures. Most patients with melanoma or breast cancer currently receive a SLN biopsy procedure that employs a non-fluorescent blue dye, Lymphazurin(R) and a Tc-99m-radioactive sulfur colloid preparation. There have been sporadic shortages of Lymphazurin(R) including its complete nationwide unavailablity for 16 months in 2006-07, possibly diminishing the nationwide quality of patient care. Vestan's approach will eliminate the need for Lymphazurin(R), avoid the up to 2% risk of anaphylactic reaction from Lymphazurin(R), eliminate the permanent tattooing of patients by Lymphazurin(R), and allow surgeons with red- green color blindness to achieve better SLN detection rates. Vestan's technology will set the groundwork for other intraoperative fluorescent technologies to lower the cost of healthcare and improve surgical outcomes worldwide, including rural and community hospitals where the access to short-lived radioisotopes for intraoperative use may not exist. PUBLIC HEALTH RELEVANCE: The use of fluorescent drugs for the location and direct visualization of lymph nodes in Sentinel Lymph Node (SLN) biopsy procedures in the operating room can replace non-fluorescent and potentially dangerous blue dyes and short-lived radioisotopes in patients undergoing an operation for breast cancer, malignant melanoma, and other types of cancer that metastasize by way of the lymphatic system. The direct fluorescent visualization technology being developed by Vestan Medical Imaging, Inc. may be superior to the current SLN biopsy procedure that employs a dark-blue dye (Lymphazurin(R)) that has undergone periodic nationwide shortages, including its unavailability for 16 months in 2006-2007, and a Tc-99m-radioactive sulfur colloid preparation. The worldwide availability of Tc-99m from a reactor in Canada or England is also tenuous. Vestan's technology has been developed to lower the cost of healthcare and improve the access to state-of-the-art healthcare worldwide. Vestan's fluorescence technology for SLN biopsy will enable rural and community hospitals that have limited access to short-lived radioisotopes to offer the best-possible surgical care to patients with cancer. Vestan has developed this technology to be inexpensive, high-impact, easy to manufacture, and commercially available within a very short time after completion of clinical trials.